Cognitive Impairment among Patients with Chronic Obstructive Pulmonary Disease Compared to Normal Individuals.

BACKGROUND
Chronic obstructive pulmonary disease (COPD) is one of the most important causes of morbidity and mortality worldwide. The complications of COPD are numerous, and cognitive impairment is one of the most common complications that relates to mortality and morbidity directly. The present study was conducted with the aim of evaluating the prevalence of cognitive impairment in patients with COPD in comparison to normal individuals.


MATERIALS AND METHODS
In this case-control study, 87 patients with COPD, whose diagnoses were confirmed by a pulmonologist based on the spirometry test findings, were included. The mini-mental state examination (MMSE) questionnaire was administered for assessing the cognitive impairment. Arterial oxygen saturation was measured. The MMSE questionnaires were administered to 60 healthy, age-and-sex-matched individuals without a history of myocardial infarction or cerebrovascular infarction, and their arterial oxygen saturations were measured. The data were analyzed using the SPSS (version 20) software.


RESULTS
In the case group, 42 patients (48.27%) had no cognitive impairment, 39 (44.82%) had mild, and 6 (6.89%) had moderate cognitive impairment. In the control group, 38 (63.33%) had no cognitive impairment, 20 (33.33%) mild and 2 (3.33 %) moderate cognitive impairment. There were significant relationships between the cognitive impairment and arterial oxygen saturation, severity of COPD, and higher age. The prevalence of cognitive impairment was 51.71% in the case group and 36.66% in the control group.


CONCLUSION
According the results of the present study, COPD increased the risk of cognitive impairment significantly and is related to the severity of COPD, arterial oxygen saturation, and higher age.


INTRODUCTION
Chronic obstructive pulmonary disease (COPD) is characterized by an irreversible limitation of pulmonary air flow and a decrease in the FEV1/FVC proportion. It is a main cause of mortality and morbidity in all countries. The most common age of onset is more than 55 years. More than 14% of individuals aged more than 65 years have COPD; an increase in its prevalence and mortality is predicted in coming decades (1). The traditional criteria for assessing the severity of COPD, such as restriction of air flow, cannot clearly define the prognosis; this is mainly Cognitive impairment is the most common extrapulmonary manifestation of COPD and is related to the mortality and disability of these patients; however, the mechanism for the same is not well understood. A systematic review reported that the cognitive function of patients with COPD is impaired in relation to normal people (2). COPD is a major risk factor for cognitive disorders (3). The prevalence of cognitive disorders in these patients has been reported to be 10% to 48%(4), and COPD can increase the risk of cognitive disorders by approximately 2.5 times(5-7). There is a direct relationship between the severity of COPD and cognitive disorders (2,(8)(9)(10). However, some studies could not find any association between COPD and cognitive disorders(1).
Concurrency of COPD and cognitive disorders leads to an increase in the mortality and hospitalization due to all causes and not pulmonary causes alone (11). In a systematic review, cognitive disorders were found in the severe form of COPD alone (12). It is known that brain hypo-perfusion occurs in patients with COPD and that an important cause for cognitive impairment is the lack of oxygen usage in hypoxemic patients (5). However, cognitive disorders have been found even in non-hypoxemic patients in some studies (13).
To have a better understanding of COPD, we need to know its complications better, including cognitive impairment. Considering the high prevalence of COPD, concurrence of cognitive impairment in these patients, and the discrepant results of different studies, we decided to assess the cognitive impairment in patients with COPD and the relation of severity of cognitive impairment using some variables, such as age, sex, arterial oxygen saturation, and use of oxygen at home.

MATERIALS AND METHODS
In this case-control study, with the ethics code were filled. An arterial oxygen saturation below 90% was considered hypoxemia. A total of 60 healthy, age-and-sexmatched people without a history of CVA or MI were referred to the pulmonologist with pulmonary complaints; COPD was ruled out by history-taking and spirometry; these individuals were considered as the control group.
The MMSE questionnaire was also administered.
All cases and controls were divided into three groups for cognitive impairment, according to the MMSE score: mild (19 ≤ score < 23), moderate (10 ≤ score < 19) and severe (score<10). T-test was done to compare the MMSE scores between the two groups and the regression test was performed to assess the relation of the above-mentioned variables with the MMSE score.

RESULTS
In the case group of 87 patients, 8  impairments. There was a significant relationship between FEV1% and the MMSE score (p-value < 0.0001) and an inverse relationship between the severity of COPD and MMSE score (p-value < 0.0001; Figure 1). To answer the question of which domains of cognition were more impaired due to the severity of COPD, bivariate and Kendall correlation analyses were performed; according to them, the relationship of the severity of COPD was significant with questions 1, 4, 5, 7, and 11; these questions were related to the time orientation, calculation, recent memory, attention, and spatial thinking, respectively ( Table 2).  these values were 36% and 12%, respectively in a study that was conducted in 2012 (2). In some studies, cognitive impairment was found in severe COPD alone (7). In the previous study that had a 20-year follow up for patients with COPD, it was shown that COPD led to a two-fold increased risk of cognitive disorders and Alzheimer disease (14). The prevalence of cognitive disorders among patients with COPD varies from 61% to 27% in different studies, according to the patient selection and severity of the disease (12,15). However, the difference in cognitive impairment between the case and control groups was not significant in some studies (10,16); this differed from the findings of our study.
Short-term hypoxemia and short-term oxygen therapy have no effect on cognitive impairment. In a study conducted on patients with COPD who experienced shortterm hypoxemia because of air travel, there was no significant change in the cognitive impairment (17). In another study, there was no change in the cognitive impairment and no improvement in driving after the use of oxygen therapy during driving in patients with COPD (18).
In a study conducted in 2010, the role of hypoxemia and home oxygen therapy in cognitive impairment was well-defined (4). A systematic review conducted in 2012 reported that there was a direct relationship between the severity of cognitive impairment, and hypoxemia and the severity of COPD; however, the effect of this cognitive impairment on the quality of life and daily activity of the patient is not understood to date (19).
In a study on hypoxemic patients with COPD, it was shown that three months of oxygen therapy led to an improvement in the cognition, blood flow in the brain, and autonomic nervous system function; however, the amount of improvement was not statistically significant for any of them (20).
In our study, a low arterial oxygen saturation was one of the most important risk factors for cognitive impairment; however, as the number of patients who used oxygen at home was low (4 of 87 patients), it was not possible to assess the relationship of oxygen therapy with cognitive impairment using statistical analysis. In a study that used magnetic resonance imaging for non-hypoxemic patients with COPD, the white matter integrity and activity of gray matter were reduced in comparison to the control group (8).
In two other studies, it was shown that even nonhypoxemic patients had significant cognitive impairment in comparison to normal people; however, this cognitive impairment did not have a considerable effect on their quality of life (9,13). In our study, there was a significant difference in the cognitive impairment between nonhypoxemic patients with COPD and the control group.
Another study reported a decrease in the cerebral blood flow of patients with COPD, especially in the frontal area, and patients had a remarkable decrease in the verbal memory, recent memory, and attention, compared to the control group. The decrease in verbal memory was found in all patients with COPD; however, the recent memory and attention impairment were only found in hypoxemic patients (10).
In the study by Antonelli-Incalzi et al., it was shown that the anterior cerebral blood flow was reduced in patients with COPD; moreover, they had impairments in